Tuesday, December 4, 2012

Organism: Entamoeba histolytica

by GP

Entamoeba histolytica is an anaerobic protozoan parasite that primarily
infects digestive tract in humans and primates.
This pathogenic microorganism is the fourth leading cause of deaths and
third leading cause of morbidity due to protozoan infections worldwide (1). Transmission of E. histolytica occurs when a person ingests food or water that is
contaminated with infected feces or during sexual intercourse (2). This sort of transmission is more prevalent
in developing countries with poor sanitary conditions. The infection of E. histolytica is usually called amebiasis or amoebiasis
(1,2). Amebiasis occurs in the large
intestines, which causes an internal inflammation. The internal inflammation is
caused by trophozoites, which are infected cells that enter the intestines. The
trophozoites come into contact with human cells, which induce a rapid influx of
calcium in the cell. This causes all
membrane movement to stop. The internal
workings of the cell are disrupted, organelles lyse and, cells die.
Consequently, the amoeba vacuums up the dead cell.

The course of infection for
this parasite starts with mature cysts entering the human body, by ingesting
mature cysts in fecally contaminated food or water.Once inside the body, trophozoites develop in
the large intestine and produce cysts. In some cases, the trophozotic cysts
could remain undetected in the intestinal lumen and pass through by feces.The cysts that exit the body by feces in cyst
form can survive outside the body for several weeks.In other cases, the trophozoites can pass the
mucosal barrier or enter the bloodstream that causes the infection to occur (2,
Figure 1). The symptoms of the disease include diarrhea and abdominal pain for
mild cases.For severe cases of the
disease the symptoms may include stomach pain, blood and mucus in feces, and
high fever (2).

Often
E. histolytica is misdiagnosed or
mistaken for other similar infections. When
diagnosing amebiasis, stool samples are usually taken and it is difficult to
distinguish if the infection is caused by E.
histolytica due to the similarity to other infections and its symptoms as
well. However, a way to determine the
presence of the parasite is to examine the number of nuclei (Figure 2). For
example, the mature cysts have four nuclei, which is a telltale sign of Entamoeba histolytica cysts. Other than
stool samples, enzyme-linked immunosorbent assay (ELISA) can be used to
evaluate the sensitivity level of the parasite in cells. ELISA is a useful tool in medicine to measure
the interaction between antibodies and antigens from foreign microorganisms.
ELISA is used to examine the trophozoites because at this stage in the cell
cycle of Entamoeba histolytica, they
are in the intestinal tract and can be easily extracted than cysts from stool
samples. The trophozoites are treated
with different detection kits for ELISA and the level of expression of each kit
are further analyzed in PCR, and this helps to know which substrate and
substance identify the pathogenic parasite.
Thus, knowing which enzyme substrate and serum substances to use for
identifying Entamoeba histolytica, the
diagnosis of the disease, amebiasis, cannot be confused by other pathogens that
share similar characteristics. Stool
samples examined under microscopy only show that parasites are present, but
cannot tell what type of parasite it is.
Treating amebiasis with proper diagnosis and antibiotics, such as
auranofin, can save lives and inform the public about how the parasite spreads.
Diagnostic steps can be taken, like using stool samples and ELISA, to ensure
the right diagnosis is made.

After
diagnosing the patient with amebiasis, there are several treatments for Entamoeba histolytic, but the rise of
antibiotic resistance is a major concern.
The treatment of amebiasis involved metronidazole, which E. histolytica is now resistant to (1)
(Oh NO!). Have no fear; new drugs are
being made to target specific sites of amebiasis. Drug screen tests have identified auranofin
as an effective drug against the parasite.
This drug is originally used for treating rheumatoid arthritis. To understand how the drug is targeting E. histolytica, transcriptional
profiling and thioredoxin reductase assays show the drug targets the parasite’s
thioredoxin reductase. Thioredoxin is a protein that acts like an
antioxidant and helps reduce other proteins by cysteine thiol-disulfide
exchange. This is an important biological process because preventing
thioredoxin reduction in E. histolytica means
disulfide bonds in cells are not reduced.
Since the disulfide bonds are not reduced, sensitivity to reactive
oxygen species (ROS) is increased in which cell structures can be damaged (1).

Along
with disrupting thioredoxin reductase, the role of adherence to mucosal
membrane is another target site for drugs (3).
As mentioned above, the course of infection mainly pertains to the large
intestines, thus the parasite seems to adhere and degrade the mucosal
barriers. Research by Ravdin et al.
found that the adherence of E.
histolytica to target cells requires microfilament function, which lyse
cells, and has a specific amebic receptor that is attracted to
N-acetyl-d-galactosamine (GALNAc) (3). The
adherence of amebas to a functional group, CHO, on cells show carbohydrate
specificity and it is a key component of the contact-mediated killing of target
cells. GALNAc inhibits the amebic
cytolysis of target cells, so cells cannot be killed. Since the cells cannot be killed, the
parasite cannot adhere to the mucosal barriers and cannot enter the bloodstream
(3,4). To target the adherence site and
adherence receptors on Entamoeba
histolytica and cell surface, respectively, drug therapies can be made to specifically
target that region, like using GALNAc.

All
the aspects of Entamoeba histolytica
is known in terms of beingthe first
human amoeba to have its genome sequenced and analyzed. The Sanger Institute is the first to sequence
the genome and with their help, further insight of the amoeba parasite can
provide evolutionary DNA markers and mechanisms of infection. The human amoeba parasite, Entamoeba histolytica, infects 50
million people around world and 70,000 deaths occur. All hands are on deck to fight Entamoeba histolytica and prevent
misdiagnosis.

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